Project Summary Conserved across all animal species, the initial cellular or humoral responses to pathogen challenge are mediated by highly conserved components of the innate immune system. While several key pathways, signaling components, and immune modulators have been described in great detail across taxa, several fundamental questions remain regarding innate immune regulation and activation. As key regulators of immune homeostasis and inflammation, bioactive signaling lipids derived from arachidonic acid collectively known as eicosanoids have integral roles in innate immune function from insects to mammals. However, despite the important role of eicosanoids in mediating cellular immune responses such as phagocytosis, encapsulation, and melanization against invading pathogens, our understanding of eicosanoid signaling in insects is limited by the lack of characterized eicosanoid receptors. Preliminary data examining the role of a candidate prostaglandin E2 (PGE2) receptor suggest that eicosanoid (prostaglandin) signaling is critical to insect innate immune responses that limit pathogen survival in the mosquito host. Therefore, the studies outlined in this proposal will characterize the putative PGE2 receptor in Anopheles gambiae (AgPGE2R) to confirm its functional role in prostaglandin signaling (Aim 1) and to examine the influence of AgPGE2R activation on mosquito cellular immune function (Aim 2). This information will provide new data into the conserved mechanisms of eicosanoid signaling to better define the immune mechanisms in which eicosanoids target and destroy pathogens in an invertebrate system.